Reaction Steps
A flask fitted with a Dean-Stark apparatus was charged with rac-(7aR,11aS)-3-hydroxy-11a-(pyridin-2-ylmethyl)-6,7,7a,8,11,11a-hexahydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridin-9(10H)-one (132, R2=Pyridin-2-ylmethyl) (6.8 g, 21.09 mmol), toluene (250 mL), ethane-1,2-diol (4.76 mL, 85 mmol) and pTSA (0.401 g, 2.109 mmol). The mixture was heated to reflux for about 2 h, cooled to rt then concentrated on under reduced pressure. The material was treated with sat. aq. NaHCO3 (50 mL), water (50 mL) and EtOAc (˜100 mL). The mixture was stirred for about 10 min then the solids were collected by filtration and washed with EtOAc (˜15 mL). The material was dried under vacuum. The filtrate layers were separated then the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic solutions were dried over MgSO4, filtered then combined with solids from the first filtration and concentrated under reduced pressure to yield rac-(7aR,11aS)-11a-(pyridin-2-ylmethyl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolan]-3-ol (143, R2=Pyridin-2-ylmethyl) (7.25 g, 94%); LC/MS, method 3, Rt=1.49 min, MS m/z 367 (M+H)+. 1H NMR (400 MHz, DMSO) δ 10.95 (s, 1H), 8.37-8.36 (m, 1H), 7.51-7.46 (m, 1H), 7.10-7.07 (m, 1H), 6.54 (s, 1H), 6.51 (d, J=7.8 Hz, 1H), 6.14 (s, 1H), 3.92-3.81 (m, 4H), 3.33 (d, J=13.3 Hz, 1H), 3.20-3.13 (m, 1H), 3.04 (d, J=13.3 Hz, 1H), 2.69-2.64 (m, 1H), 2.14-2.06 (m, 1H), 2.04-1.96 (m, 1H), 1.91-1.77 (m, 1H), 1.75-1.47 (m, 7H), 1.41-1.23 (m, 1H).
